Safety and Tolerability of Single and Multiple Doses of ISIS 353512 in Healthy Volunteers

Ionis Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Inflammatory Diseases

Treatments

Drug: ISIS 353512

Study type

Interventional

Funder types

Industry

Identifiers

NCT00734240

ISIS 353512 CS1

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of single and multiple doses of ISIS 353512, to evaluate the blood concentration and rate elimination of ISIS 353512 from the blood, and to evaluate the effectiveness of ISIS 353512 in lowering a protein in the blood associated with inflammation.

Full description

This will be a Phase 1, double blind, placebo-controlled, dose-escalation study conducted at a single center to 1)evaluate the safety and tolerability of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously, 2)evaluate the pharmacokinetic profile of single and multiple doses of ISIS 353512 administered intravenously and subcutaneously, and 3)evaluate the pharmacodynamics of ISIS 353512 in lowering constitutive levels of c-reactive proteins in healthy volunteers.

Enrollment

103 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Age 18 to 55 years
Male or female although females must be post-menopausal or surgically sterile
In good health
BMI < 32 kg/m2
Give written informed consent to participate in the study
hsCRP at Screening ≥ 0.50 mg/L and ≤ 5.0 mg/L (for 2 measurements ≥ 2 weeks apart; with difference between measurements ≤ 2.5 mg/L)(Multiple Dose Subjects only, not including dose-titration cohorts)

Exclusion criteria

Pregnant women, nursing mothers or women of childbearing potential
Clinically significant abnormalities in medical history or physical examination
Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood pressure < 90 mm Hg or > 140 mm Hg, diastolic blood pressure < 50 mm Hg or > 90 mm Hg or heat rate < 50 or > 100 bpm) at Screening
Clinically significant abnormalities on laboratory examination, other than hsCRP
Clinically significant abnormalities in coagulation parameters
Positive test for HIV, TB (PPD test) or hepatitis B or C at Screening
History of latent or active tuberculosis or exposure to endemic areas within 8 weeks prior to PPD test at Screening
History of positive PPD test or positive PPD test result (≥ 5 mm) indicating possible tuberculosis infection
Fasting triglycerides > 400 mg/dL at Screening
Malignancy (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for > 1 year)
Evidence of ongoing chronic inflammatory condition or infection
Any other concurrent condition which, in the opinion of the Investigator, would preclude participation in this study or interfere with compliance
Regular use of alcohol within 6 months prior to Screening (> 14 units of alcohol per week; 1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol)
Use of soft drugs (such as marijuana) within 3 months prior to Screening or hard drugs (such as cocaine, phencyclidine [PCP] and crack) within 1 year prior to Screening, or positive urine drug screen at Screening
Smoking > 10 cigarettes per day
Use of an investigational drug or participation in an investigational study involving a small molecule with 30 days prior to dosing or participation in an investigational study involving biologic compounds within 90 days prior to dosing
Regularly taking OTC medications and/or vitamin supplements that may alter CRP, e.g., NSAIDs, aspirin, vitamin E, fish oil, within 14 days prior to Screening
Receiving prescription medications, including hormone replacement therapy, statins, TNF-α inhibitors, or other anti-inflammatory or immunosuppressive drugs within 30 days prior to Screening
Immunization with a live attenuated vaccine one month prior to dosing or planned vaccination during the course of the study
Blood donation of 50 to 499 mL within 30 days of Screening or of > 499 mL within 60 days of Screening

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Single Group Assignment

Masking

Triple Blind

103 participants in 16 patient groups

Experimental group

Description:

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 355312 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

single-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Experimental group

Description:

multiple-dose cohort (n=4, randomized 3 active : 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

F (100 mg)

Experimental group

Description:

single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Dose-Titration 1

Experimental group

Description:

multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

F (200 mg)

Experimental group

Description:

single-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Dose-Titration 7

Experimental group

Description:

multiple-dose cohort (n=4, randomized 3 active: 1 placebo) receiving ISIS 353512 or placebo

Treatment:

Drug: ISIS 353512

Trial contacts and locations

Data sourced from clinicaltrials.gov

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